ENDOTHELIN RECEPTOR SUBTYPES IN HUMAN VERSUS RABBIT PULMONARY-ARTERIES

We studied which endothelin (ET) receptor subtypes mediate ET-1-induce d vasocontraction in the human pulmonary artery (PA) compared with the rabbit PA. ET-1 produced potent contraction in both human and rabbit isolated PAs. In human PA, ET-1-induced contraction was competitively antagonized by BQ-123 (an ET(A) receptor antagonist) with a pA(2) valu e of 7.68. In rabbit PA, however, even a high concentration of BQ-123 (1 mu M) did not affect the contraction. BQ-3020 (an ET(B) receptor ag onist) produced potent contraction in rabbit PA but not in human PA. B inding assays of the membrane preparations showed that human and rabbi t PAs contained ET(A) and ET(B) receptors in ratios of 93:7 and 23:77, respectively. These results suggest interspecies differences in the E T receptor subtypes that mediate ET-1-induced vasocontraction; ET(A) r eceptors are dominant in the human PA, whereas ET(B) receptors are dom inant in the rabbit PA. Furthermore, the predominance of ET(A) recepto rs in human PA was supported by autoradiographical studies. If ET-1 ac ts as a physiological and/or pathophysiological vasocontractor in the human pulmonary circulation, an ET(A) receptor antagonist would functi on as a pulmonary vasodilator in humans.